2-(2&#39;, 5&#39;-dialkoxybenzyl)-2-imidazolines and related compounds



United States Patent 9 Claims. erase-309.6

This invention relates to improved pi'lomotor agents, particularly useful for pre-sh aving lotions, and to an improved method of shaving.

For the preparation of the skin before shaving, particularly dry shaving by electric razors, it has recently become customary to use agents which temporarily cause the whiskers to rise and protrude from the skin surface. Through the use of such pilomotor substances, the whiskers are more effectively seized and are cut off directly on the skin surface by the cutting edges of the razor.

Although the previously known pilomotor substances are somewhat effective in facilitating the shaving operation, there is still a need for more powerful agents to make the whiskers snap to attention.

'The principal object of this invention, therefore, is to provide more efficacious pilornotor agents for pretrcating the skin before shaving.

Another object is to provide novel pre-shaving lotions.

Still another object is to provide a method of shaving.

Still other objects and advantages of this invention will become apparent upon further study of the specification and appended claims.

I These objects are attained by the unexpected discovery that ex'ceptionally'high pilomotor activities are exhibited by imidazoline derivatives of the formula:

wherein n is integer from 0 to 1, and

R alternatively represents napht-hyl, tetrahydronaphthyl, benzothienyl, and indanyl, or a phenyl, naphthyl, tetrahydronaphthyl, benziothienyl, and indanyl radical substituted by one or more moieties of the group containing hydroxyl, alkyl of 1-4 carbon atcms,'methoxy and ethoxy. It is preferred that the upper limit of the number of such moieties is five.

Exemplary of these compounds are:

2-(2',5'-dimethoxybenzyl)-2-imidazo1ine; M.P. 96 C.

2- 2',5 '-dimethoxy-4'-methylbenzyl -2-imidazoline;

M.PJ 96-97 C. i i

2- 2,5-dimethoxy-4-ethylbenzyl) -2-imi dazoline;

M.P. 94 C.

2-( 2,5-dimethoxy-4,6'-dimethylbenzyl) -2-imidazoline;

M.P. 120l21 C.

2- (2',5-dimethoxy-3 ,4',6'-trimethylbenzyl) -2- imidazoline; M.P. 185l86 C.

2-(2',5'-diehhoxybenzyl)-2-imidazoline; M.P. of the hydrochloride: 180 C.

2- 2',5'-dirnethoxy-3 ,6'-dimethylbenzyl) -2-imidazoline;

M.P. 152 C.

2- 2',5 -diet hoxy-4,6'-dimethylbenzyl -2-imidazo'line;

2-(3,5-dimethoxybenzyl)-2-imidazoline; M.P. of the hydrochloride: 162164 C.

2-(2,3',4'-trimethoxybenzyl)-2-irnidazoline;-

2-(2,4',5'-trimethoxybenzyl) -2-imi=d-azoline; M.P.

"ice

2-(3,4,5',-trimethoxybenzyl)-2-imidazoline; M.P. of the hydrochloride: 184185 C.

2- (3 ,4',5 '-triethoxybenzy-l -2-imidazoline;

2- 2,6-dimethyl-4-tert.butylbenzyl) -2-imidazoline;

M.P. 131-133" C.

2- (2',6 '-dimethyl-3 -thydroxy-4'-tert.butylb enzyl) -2- imidazoline; M.P. 180l82 C. 2-(naphthyl-l-methyl)-2-imidazoline; M.P. of the hydrochloride: 255-260 C. 2-(2'-methylnaphthyl-1-methyl) -2-imidazoline;

2- (2'-rnethoxynaphthyl-1-methyl -2-imidazoline; M.P.

147l48 C. 2-(4-methoxynaphthyl-lsmethyl)-2-imidazoline; M.P.

Z-(indanyl-l')-2-imidazoline; M.P. of the hydrochloride- 2-( 1',2',3 ,4'-tetrahydronaphthyl-1')-2-imidazoline;

imidazoline; M.P. 162-164 C.

2- 2'-methylbenzothienyl-3'-methyl -2-imidazoline; M.P.

l56-157 C. and

2-(benzothieny-l-3-methyl)-2-imidazoline; M.P. of the hydrochloride: 234235' C.

To prevent any confusion as to the numbering system employed, the structuralformula of 2 -(2,5'-'di-rnethoxybenzyl)-2-imidazoline, is as follows:

(FCH;

don,

In comparison to what is believedto be the best pilomotoricum now on the market, 2-(3',4-dihydroxyphenyl)- morpholino-hydrochloride (in the following named A), the compounds of the present invention have a considerably increased pilomotoreffect. For example, the 2- (l,2',3,4'-tetrahydronaphthyl-1)-2-imidazoline and the 2-(2',5-dimethoxy-4'-methylbenzyl)-2-imidazoline exhibit a 3-fold higher effect; the 2-(3',5'-dimethoxy-benzyl)-2- imidazoline 7-fold higher; the 2-(naphthyl-1-methyl)-2- imidazoline and the 2-(2,6-dimethyl-3'-hydroXy-4'-tert.-

butylbenzyl)-2-imidazoline 10-fold higher; the 2-(2,5'-dimethoxy-Z',4',6'-trimethyl-benzyl)-2-imidazoline 2 5 fold higher; the 2-(2,5-dimethoxybenzyl)-2-imidazoline 57- fold higher; and the 2-(2',5'-dimethoxy-4',6'-dimethylbenzyl)-2-imi-dazoline 133-fold higher pilomotor effect than the substance A. p

The pilomotor effectiveness of the novel compounds Was tested according to the following method.

Rats were shaved on their backs. The shaved spot was washed with soap and lukewarm Water and dried. About /2 hour later, the test solution was applied in the following manner: 7

Three parallel sections (length and width about 5-7 mm.) were moistened, from the cranial to the caudal parts of the rat, with a piece of cotton wool the size of a pea impregnated with 0.2 ml. of the test solution. In comparison to the unmoistened area, a rising of the hair is noticed. The minimal concentration showing a pilomotoric efiect is determined. This concentration of substance A is defined as standard: 1, the corresponding concentrations of the other substances are referred to this value.

All test materials were dissolved in water and adjusted to a pH value of 56 with dilute aqueous hydrochloric acid. This method of testing is new and results in more readily reproducible values, confirmed in practice, than the so-called cat-tail test ordinarily used for testing the pilomotor effectiveness of chemical compounds.

The pilomotor-effective compounds, according to this invention, can be used in the free form or in the form of their physiologically compatible acid addition salts, e.g., in the form of thier hydrochlorides, hydro-bromides, sulphates, citrates or succinates. It is advantageous to employ pilomotor substances in the form of solutions, using such suitable solvents as, for example, mixtures of water with ethanol or isopropanol.

It is also advantageous to admix to the solutions physiologically compatible acids, such as adipic acid, citric acid or tartaric acid, or acid-hydrolyzing salts, such as zinc chloride or aluminum chloride, the last mentioned salts additionally exhibiting an astringent effect on the skin. Moreover, it is possible to add to the novel pilomotorica, conventional dissolving aids such as lactic acid-diethylamide, or skin care agents, or agents for increasing the lubricating properties of the skin, such as propylene glycol, isopropyl myristate, or astringents, such as hamamelis extract or menthol, or antiseptic susch as camphor, 8-hydroxyquinoline sulfate or p-hydrobenzoic acid, as well as perfumes.

A further advantage of the novel pilomotor-efiective compounds is that they are stable in an alkaline medium as well as in an acid medium. It is this fact that permits their use in wet shaving, as well as for electric shaving, since the shaving soaps generally employed exhibit an alkaline reaction.

For dry shaving, a lotion may be composed as follows:

For Wet shaving, a formulation may include:

Percent by weight Ingredient General Preferred Pilornotor substance of the invention 0. 001-1. 0. 01-0.

van 3-95 5-85 Physiologically compatible acid 'or acid-hydrolyzing salt 0-15 5-10 Diss'olving aids 0-5 1-3 Skin care agents 0-10 0. 01-5 Skin lubricating agent 5-95 20-80 Astringent 0- 5 2-3 Perfume 0. 01-5 0. 05-3 Some of the pilomotor-effective substances of this invention are known, per se, but their utilization as pilomotor agents is neither suggested nor predictable, much less is there the remotest indication in the literature that they would be many fold more efiective than the pilomotorica presently on the market. The pilomotor-efiicaciousness of the agents 'of this invention is thus truly new and unexpected.

Of the various pilomotor effective compounds of this invention, the following are also novel, per se.

2- 2,5 '-dimethoxy-4'-ethylb enzyl) -2-imidazoline;

.M.P. 94 C.

2- (21,5 '-dirnethoxy-4C,6-dimethy1benzyl) -2-imidazoline;

M.P. 120-121 C.

2- (2,5 -dimethoxy-3 ,4-6'-trirnet-hylbenzyl) -2-imidazoline; M.P. ll86 C.

2-(2',5'-diethoxybenzyl)-2-irnidazoline; M.P. of the hydrochloride: C.

2- (2',5 -dimethoxy-3 ',6'-dimethylbenzyl) -2-imidazoline;

M.P. 152 C.

2- (2,5 -diethoxy-4'-6'-dimethylbenzyl) -2-imidazoline;

2-(3',5-dimethoxybenzyl)-2-imidazo1ine; M.P. of the hydrochloride: 162-164 C.

2-( 5 ,8'-dimethoxyl ,2,3 ,W-tetrahydronaphthyl-1')-2- imidazoline; M.P. 162164 C.

These novel compounds can be produced by condensing a carboxylic acid of the formula R(CH COOH or one of the functional derivatives thereof, with ethylenediamine or with ethylenediamine-yielding agents (see for example, German Patent 1,117,588).

Without further elaboration, it is believed that one skilled in the art, can, using the preceding description, utilize the present invention to its fullest extent. The following preferred specific embodiments are, therefore, to be construed as merely illustrative, and not limitative, of the remainder of the specification and claims in any way whatsoever.

Example 1 G. 2-(2',5'-dimethoxybenzyl) -2-imidazoline 0.1 2 N hydrochloric acid 0.5 Citric acid 2.0 Aluminum chloride cryst 0.5 Polyvinyl pyrrolidone 0.5 Isopropyl myristate 5.0 96% alcohol 80.0 Water and perfume, ad 100.0

Example 2 G. 2-(2',5'-dimethoxybenzyl)-2-imidazoline 0.1 Citric acid 2.5 Polyvinyl pyrrolidone i 0.5 Isopropyl myristate 3.5 96% alcohol 80.0 Water and perfume, ad 100.0

Example 3 G. 2 (2',5' dimethoxy-4',6-dirnethylbenzyl)-2-imidazoline 0.03 2 N hydrochloric acid 0.5 Citric acid 2.0 Isopropyl myristate 5.0 96% alcohol 80.0 Water and perfume, ad. 100.0

Example 4 G. 2 (2,5' dimethoxy-4',6'-dimethylbenzyl) -2-imidazoline 0.02 Tartaric acid 1.5 Boric acid 1.5 Propylene glycol 2.0 96% alcohol 60.0 Water and perfume, ad 100.0

Example 5 G. 2 (naphthyl 1-methyl)-2-imidazoline-hydroch1oride -1 0.5 Citric acid 1,5 Boric acid -i 1.5 Propylene glycol Y 2.0 96% alcohol 50.0

Water and perfume, ad 100.0

Example 6 G. 2 (naphthy1- 1'-methyl)-2-imidazoline-hydroch1oride 0.5 Citric acid 2.0 Polyvinyl pyrrolidone 0.5 Mixture of higher molecular quaternary ammonium compounds as surface active agent 0.5 96% alcohol 50.0 Water and perfume, ad 100.0

Example 7 G. 2 (2,5'-dimethoxy-3',4,6'-trimethylbenzyl)-2-imidazoline 0.2 2 N hydrochloric acid 0.5 Citric acid 2.0 Aluminum chloride cryst 0.5 Isopropyl myristate 5.0 96% alcohol 80.0 Water and perfume, ad. 100.0

Example 8 G. 2 (2,5-dimethoxy-3,4,6'-trimethylbenzyl) -2-imidazoline 0.2 Polyvinyl pyrrolidone 1.0 Mixture of higher molecular quaternary ammonium compounds as surface active agents 0.5 2 N hydrochloric acid 0.5 96% alcohol 50.0 Water and perfume, ad. 100.0

Example 9 G. 2 (1',2,3',4 tetrahydronaphthyl-l')-2-imidazoline-hydrochloride 0.7 Tartaric acid 1.5 Boric acid 1.0 Propylene glycol 3.0 96% alcohol 60.0 Water and perfume, ad. 100.0

Example 10 G. 2 (2' methylbenzothieny1-3'-methyl)-2-imidazoline-hydrochloride 0.3 Citric acid 2.0 Isopropyl myristate 3.0 Propylene glycol 1.0 Isopropanol 75.0 Water and perfume, ad. 100.0

Example 11 G. 2 (4-tert. butyl-3'-hydroxy-2',6'-dimethylbenzyl) 2-imidazoline-hydrochloride 0.3 Tartaric acid 1.5 Boric acid 1.5 Propylene glycol 2.0 Isopropanol 50.0 Water and perfume, ad. 100 .0

Example 12 2- 2',5'-diethoxy-4',6'-dimethylbenzyl) -2- G.

imidazoline-hydrochloride 0.5 Citric acid 0.5 Isopropyl myristate 3.0 Menthol 0.1

Isopropanol 75.0

Water and perfume, ad 100.0

Example 1 3.-Brushless shaving cream 2-(2',5-dimethoxy-4',6'-dimethylbenzyl)- Percent Z-imidazoline 0.05 Stearic acid 12.6

Triethanolamine 1.0 40% aqueous potassium hydroxide solution (freshly prepared) 1.2 Polyethyleneglycol 15.1 Sodium alginate 1.2 1,2-propanediol 4.0 70% aqueous sorbitol solution 5.0 Perfume oil 0.5 Distilled water, q.s 100.0

Example I4.Lather-shaving-cream 2- 2,5'-dimethoxy-4,6'-dimethylbenzyl)- Percent 2-imidazoline 0.05

Stearic acid 36.0

Peanut oil 8.3 Olive oil 1.2 Sodium hydroxide 1.0 Potassium hydroxide 7.9 1,2-propanedi0l 3.3 Glycerol 2.0 Perfume oil 0.5 Distilled water, q.s. 100.0

Example 15.--Shaving jelly 2-(2',5'-dimethoxy-4,6'-dimethylbenzyl)- Percent 2-imidazoline 0.05

Glycerol 5.0 Gum tragacanth 5.0 Ethanol 15.0 Boric acid 1.0 Perfume oil 0.5 Distilled Water, q.s. 100.0

The following example is a preferred embodiment for the method of preparing the novel imidazoline compounds of this invention:

11.5 grams of 2,5-dimethoxybenzyl cyanide (prepared according to E. Baumann and S. Frakel, Hoppe-Seylers Zeitschrift fiir physiologische Chemie, volume 20 (1895), page 219; MP. 5455 C.) and 22.6 g. of the mono-ptoluene-sulfonate of ethylene diamine are heated together in an oil-bath at approximately 200 C. bath temperature for 2 hours. The reaction product is allowed to cool, and about 50 cc. of 16% sodium hydroxide solution is added to it. The 2- (2.5-dirneth0xybenzyl)-2-imidazoline is thus precipitated as an oil. The base is taken up in about 50 cc. of chloroform, and the aqueous solution is extracted three times more with 50 cc. of chloroform. The combined chloroform extracts are washed with about cc. of water and concentrated. The resinous residue is distilled in high vacuum. The fraction which boils at 143- 145 C./ 0.01 mm. contains the desired base which is recrystallized from acetone or acetone/petroleum ether; the compound melts at 94-95 C. Yield 9.5 g. 66% of the theoretical. By adding of ethanolic hydrogen chloride to the base and recrystallization of the salt from ethanol/ ether, the 2-(2.5-dimethoxybenzyl)-2 imidazoline hydrochloride, MP. C., is obtained From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions. Consequently, such changes and modifications are properly, equitably, and intended to be, within the full range of equivalence of the following claims.

What is claimed is:

1. 2-(2',5'-dimethoxy-4'-ethylbenzyl)-2-imidazoline.

2. 2-(2',5' dimethoxy 4',6' dimethylbenzyl)-2-imidazoline. 

6. 2-(2'',5''-DIETHOXY-4'',6''-DIMETHYLBENZYL)-2-IMIDAZOLINE.
 8. 2-(5'',8''-DIMETHOXY-1'',2'',3'',4''-TETRAHYDRONAPHTHYL1'')-2-IMIDAZOLINE.
 9. 2-(2'',5''-DIMETHOXYBENZYL)-2-IMIDAZOLINE. 